Figure 2. Validation, conservation, and position of the SMARCA4 mutation.

(A) Sanger sequencing results of an affected individual heterozygous for the SMARCA4 mutation and an unaffected individual with the wild-type allele. (B) Multiple sequence alignment of SMARCA4 orthologues with percentage of protein sequence identity between the human protein and several mammalian proteins. Black box marks the position of the Glutamate residue mutated to Lysine. Symbols below sequences correspond to degree of conservation: asterisk indicates identical; period indicates weakly similar; blank indicates no similarity. (C) Illustration of the various subunits composing the PBAF complex[28], a member of the human SWI/SNF family of chromatin remodelers. The catalytic subunit of the complex, BRG, is encoded by SMARCA4 (highlighted in green). (D) Schematic representation of BRG1 showing all conserved domains of the protein, with approximate corresponding positions indicated below; information obtained from SMART protein domain annotation resource[46]. Arrow marks the site of the altered amino acid in residue 1610, adjacent to the Bromodomain. Domain names: QLQ, a Gln, Leu, Gln motif; HSA, helicase/SANT-associated; BRK, brahma and kismet; DEXDc, DEAD-like helicases superfamily; HELICc, helicase superfamily c-terminal domain; SnAC, Snf2-ATP coupling, chromatin remodeling complex; BROMO, bromodomain.